Synthesis and characterization of copper(II) complex derived from newly synthesized acenaphthene quinone thiosemicarbazone ligands: Computational studies, in vitro binding with DNA/BSA and anticancer studies

Three Cu(II) complexes (CTS1-CTS3) of acenaphthene quinone thiosemicarbazone with various N-terminal substitutions were synthesized. The prepared compounds were characterized via different spectroscopic analyses. The square planar structure formed by the ligands with Cu(II) (tridentate manner, ONS donor) is confirmed through EPR spectral analysis. The DNA binding studies performed using UV–visible and fluorescence spectroscopy point out that, all complexes showing significant interaction with DNA and CTS2 were the strongest (K_b = 6.46 × 10⁶ M⁻¹ & K_app = 2.5 × 10⁶ M⁻¹). A similar binding trend is observed towards the BSA protein (CTS2 with high K_b value, 1.76 × 10⁵ M⁻¹). The docking studies with EGFR protein (PDB ID: 5EDQ) reveal that CTS2 has the highest affinity towards them with a docking energy of − 7.41 Kcal/mol. The DFT investigations account for the stability (CTS3 has better structural stability with a high band gap, 0.10634 eV) and biological activity of complexes (CTS2 has a stronger biological activity due to its low ω value, 0.5864 eV). The lipophilicity (LogP ˃ 5) values obtained via Swiss-ADME studies are satisfactory and indicate that all 3 complexes have the potential to function as good oral drug candidates. The MTT assay results showed that CTS2 was the most effective against human breast (MCF-7), lung (A549), and cervical (HeLa) cancer cell lines, with IC₅₀ values of 11.5, 43.9, and 19.6 μM, respectively. Conversely, CTS2 showed the least cytotoxicity (IC₅₀ = 79.7 μM) when it came to normal (Vero) kidney epithelial cells.